Lifestyle interventions for acute gout

  • Review
  • Intervention

Authors

  • John HY Moi,

    Corresponding author
    1. The Royal Melbourne Hospital, Department of Rheumatology, Parkville, Victoria, Australia
    • John HY Moi, Department of Rheumatology, The Royal Melbourne Hospital, Grattan Street, Parkville, Victoria, 3050, Australia. john.moi@mh.org.au.

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  • Melonie K Sriranganathan,

    1. University Hospital Southampton NHS Foundation Trust, Department of Rheumatology, Southampton, Hampshire, UK
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  • Christopher J Edwards,

    1. University Hospital Southampton NHS Foundation Trust, Department of Rheumatology, Southampton, Hampshire, UK
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  • Rachelle Buchbinder

    1. Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Monash Department of Clinical Epidemiology, Cabrini Hospital, Malvern, Victoria, Australia
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Abstract

Background

Although lifestyle interventions are often recommended in the management of chronic gout, the evidence from trial data of the benefits and safety of using lifestyle interventions for treating acute gout attacks have not previously been examined in a systematic review.

Objectives

The objective of this systematic review was to evaluate the benefits and safety of lifestyle interventions for the treatment of people with acute gout.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE for studies (up to 5 April 2013). We also searched the 2010 to 2011 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) abstracts and performed a handsearch of the reference lists of included articles.

Selection criteria

Studies were included if they were randomised or quasi-randomised controlled trials which compared lifestyle interventions to another therapy (active or placebo) in patients with acute gout. Outcomes of interest were the change in participant-reported pain in the target joint(s), target joint inflammation and function, health-related quality of life (HRQoL), patient global assessment, study participant withdrawals due to adverse events (AEs) and serious adverse events (SAEs).

Data collection and analysis

Two review authors independently applied methods recommended by The Cochrane Collaboration for the selection, appraisal, data collection and synthesis of studies. We assessed the quality of the body of evidence for each outcome using the GRADE approach.

Main results

Only one study (19 participants) at high risk of bias was included in the review. Patients were randomised to receive oral prednisolone and colchicine with or without concomitant topical ice therapy. Topical ice therapy provided significant additional benefit over oral prednisolone and colchicine alone with respect to pain, but did not significantly reduce swelling during acute gout episodes. Mean pain reduction with standard medical treatment was 4.4 cm on a 0 to 10 cm visual analogue scale (VAS) after one week; the addition of topical ice reduced pain by an additional 3.33 cm (95% CI 5.84 to 0.82), or an absolute reduction of 33% (8% to 58% reduction). Joint swelling was reduced by a mean of 3.8 cm in the standard medical treatment group; the addition of topical ice therapy did not reduce swelling significantly (mean difference (MD) 2.07 cm, 95% CI -1.56 to 5.70). Target joint function, HRQoL, patient global assessment, study participant withdrawals due to AEs and SEAs were not reported in this study.

Authors' conclusions

There is low quality evidence, from a single trial at high risk of bias, that the addition of topical ice therapy to oral prednisolone and colchicine for oligoarticular attacks of acute gout results in significantly greater pain reduction at one week.

Résumé scientifique

Interventions axées sur le mode de vie pour les crises de goutte aiguë

Contexte

Bien que les interventions axées sur le mode de vie soient couramment recommandées dans la prise en charge des patients souffrant de goutte chronique, les preuves issues des données des essais en faveur de leurs bénéfices et de leur sécurité n'ont jamais été examinées dans une revue systématique.

Objectifs

L'objectif de cette revue systématique était d'évaluer les bénéfices et l'innocuité des interventions axées sur le mode de vie pour le traitement des personnes souffrant de goutte aiguë.

Stratégie de recherche documentaire

Nous avons effectué des recherches dans le registre Cochrane des essais contrôlés (CENTRAL), MEDLINE et EMBASE pour les études (jusqu' au 5 avril 2013). Nous avons également effectué des recherches dans les résumés 2010 et 2011 de l’American College of Rheumatology (ACR) et de la Ligue européenne contre le rhumatisme (EULAR), ainsi que des recherches manuelles dans les bibliographies d’articles inclus.

Critères de sélection

Les études ont été incluses s'il s'agissait d'essais contrôlés randomisés ou quasi-randomisés (ECR ou ECC) ayant comparé des interventions axées sur le mode de vie à un autre traitement (actif ou placebo) chez les patients souffrant de goutte aiguë. Les critères intéressants ont été les changements de la douleur rapportée au niveau des articulations ciblées, une inflammation de l’articulation ciblée, les capacités fonctionnelles et la qualité de vie liée à la santé (QVLS), l'évaluation globale du patient, les arrêts prématurés des participants en raison d'effets indésirables (EI) et les effets indésirables graves (EIG).

Recueil et analyse des données

Deux auteurs de la revue ont indépendamment appliqué les méthodes recommandées par la Collaboration Cochrane pour la sélection, l'appréciation, le recueil des données et la synthèse des études. Nous avons évalué la qualité de l'ensemble des preuves pour chaque critère de jugement en utilisant l'approche GRADE.

Résultats principaux

Une seule étude (19 participants) présentant un risque de biais élevé a été inclue dans la revue. Les patients étaient randomisés pour recevoir du prednisolone et de la colchicine par voie orale avec ou sans traitement par glace topique. Le traitement par glace topique apportait un bénéfice supplémentaire significatif par rapport au traitement seul au prednisolone et à la colchicine en ce qui concerne la douleur, mais n'a pas significativement réduit le gonflement au cours des crises de goutte aiguë. La réduction de la douleur moyenne avec un traitement médical standard était de 4,4 cm sur une échelle visuelle analogue (EVA ) de 0 à 10 cm après une semaine; l'ajout de glace topique réduit la douleur de 3,33 cm supplémentaire (IC à 95% de 5,84 à 0,82), ou une réduction absolue de 33% (8% à 58% de réduction). Le gonflement des articulations a été réduit par une moyenne de 3,8 cm dans le groupe de traitement médical standard; l'ajout de glace topique n'a pas permis de réduire le gonflement de manière significative (différence moyenne (DM) 2,07 cm, IC à 95% de -1,56 à 5,70). L’articulation ciblée, la QVLS, l'évaluation globale du patient, les arrêts prématurés des participants dus à des EI et EIG n'étaient pas rapportés dans cette étude.

Conclusions des auteurs

Un seul essai, avec des preuves de faible qualité et un risque de biais élevé, montre que l'ajout de glace topique au traitement par prednisolone et par colchicine pour les crises oligo-articulaires de goutte aiguë résulte d’une baisse significative de la douleur à une semaine.

Resumo

Mudanças no estilo de vida no tratamento de crises de gota aguda

Introdução

Embora mudanças no estilo de vida sejam frequentemente recomendadas no tratamento da gota crônica, as evidencias sobre os benefícios e a segurança do uso de mudanças no estilo de vida no tratamento de crises de gota aguda não foram avaliadas em uma revisão sistemática.

Objetivos

O objetivo desta revisão sistemática foi avaliar os benefícios e a segurança da mudança de estilo de vida para o tratamento de pessoas com gota aguda.

Métodos de busca

Nós buscamos no Cochrane Central Register of Controlled Trial (CENTRAL), MEDLINE e EMBASE por estudos (a partir de 5 de abril de 2013). Nós também buscamos nos resumos de 2010 a 2011 American College of Rheumatology (ACR) e Europe League Against Rheumatism (EULAR) e realizamos uma busca manual sobre listas de referências dos artigos inclusos.

Critério de seleção

Estudos foram inclusos se eles foram randomizados ou parcialmente randomizados, os quais compararam mudanças nos estilos de vida com outras terapias (ativo ou placebo) em pacientes com gota aguda. Desfechos de interesse foram as alterações na dor relatada pelo participante na articulação acometida(s), na inflamação da articulação e na função, qualidade de vida relacionada à saúde, avaliação global do paciente, excluídos do estudo participantes com eventos adversos e eventos adversos graves.

Coleta dos dados e análises

Dois autores revisores independentes aplicaram os métodos recomendados pelo Cochrane Collaboration para seleção, avaliação, coleta de dados e resumo de estudos. Avaliamos a qualidade do corpo de evidencias para cada resultado, usando a abordagem GRADE.

Principais resultados

Somente um estudo (19 participantes) de elevado risco de viés foi incluído na revisão. Pacientes foram randomizados para receber prednisolona oral e colchicina com ou sem terapia de gelo tópico concomitante. Terapia do gelo tópico promoveu significante beneficio adicional em relação a prednisolona e colchicina apenas no que diz respeito à dor, mas não apresentou significativa redução do inchaço durante os episódios de gota aguda. A significante redução da dor com o tratamento médico padrão foi 4,4 cm de 0 a 10 cm em uma escala análoga visual após uma semana; a adição de gelo tópico reduziu a dor em um adicional de 3,3cm (95% intervalo de confiança 5,84 para 0,82), ou uma redução absoluta de 33% (8% a 58% de redução). Edema da articulação foi reduzido por um significante 3,8 cm no grupo do tratamento medico padrão; a adição da terapia do gelo tópico não reduziu o edema significativamente (diferença significativa 2,07 cm, 95% intervalo de confiança – 1,56 a 5,70). Função da articulação acometida, qualidade de vida relacionada à saúde, avaliação global do paciente, exclusão de participantes por efeitos adversos e efeitos adversos graves não foram reportados neste estudo.

Conclusão dos autores

Há poucas evidencias de qualidade, a partir de um estudo simples com alto risco de viés, que a adição da terapia do gelo tópico à prednisolona e à colchicina para crises oligoarticulares na gota aguda resulta em redução significativamente maior da dor em uma semana.

Notas de tradução

Traduzido por: Marcelo Zerbetto Fabricio, Unidade de Medicina Baseada em Evidências da Unesp, Brazil Contato: portuguese.ebm.unit@gmail.com

アブストラクト

急性痛風発作に対する生活習慣への介入効果

背景

生活習慣への介入は、しばしば慢性痛風に対する治療として推奨されるが、急性痛風発作の治療としての生活習慣介入における有益性および安全性を調べた研究データによるエビデンスは、これまでにシステマティック・レビューとして検討されていない。

目的

本システマティック・レビューの目的は、急性痛風発作患者の治療における生活習慣介入の有益性および安全性を評価することであった。

検索戦略

Cochrane Central Register of Controlled Trials (CENTRAL)、MEDLINEおよびEMBASEを検索した (2013年4月5日まで)。また、2010年~2011年に開催された米国リウマチ学会(ACR)および欧州リウマチ学会(EULAR)のアブストラクトを検索し、論文の参考文献リストをハンドサーチした。

選択基準

急性痛風発作患者を対象とし、生活習慣介入とその他の治療法(実薬もしくはプラセボ)を比較したランダム化または準ランダム化比較試験をレビュー対象とした。注目したアウトカムは、参加者からの自己報告による罹患関節の疼痛の変化、罹患関節の炎症および機能、健康関連のQOL(HRQoL)、患者による全般的評価、有害事象(AE)および重篤な有害事象(SAE)による試験参加者の中止例であった。

データ収集と分析

コクラン共同計画が推奨している手法を用いて2名のレビュー著者が独立して試験の選択、評価、データ収集および統合を実施した。GRADE方法論に沿って、各アウトカムについて中心となるエビデンスの質を評価した。

主な結果

高いバイアスのリスクを示した1件の試験(参加者19例)のみがレビュー対象となった。患者は、経口プレドニゾロンおよびコルヒチンの単独投与群と局所冷却療法との併用群に無作為に割り付けられた。局所冷却療法は、経口プレドニゾロンおよびコルヒチン単独に比べて、疼痛に関して有意な有益性が認められたが、急性痛風発作が起きている間の腫脹の軽減は有意ではなかった。標準治療を1週間実施した疼痛緩和の平均値は、0~10 cmの視覚的アナログ尺度(VAS)で4.4 cmであった。局所冷却療法を追加した場合の疼痛緩和は、さらに3.33 cm長く(95% CI 5.84~0.82)、その絶対的減少は33%に相当した(8%~58%の緩和)。関節の腫脹は、標準治療群では平均3.8 cm軽減された。局所冷却療法の追加による腫脹の軽減は有意ではなかった(平均差[MD]2.07 cm、95% CI -1.56~5.70)。罹患関節の機能、HRQoL、患者による全般的評価、AEおよびSAEによる試験参加者の中止例は、本試験では報告がなかった。

著者の結論

高いバイアスのリスクを示した1件の試験からエビデンスが得られたが、エビデンスの質は低かった。少数の関節で認められた急性疼痛発作に対して、経口プレドニゾロンおよびコルヒチンに局所冷却療法を追加した結果、1週間で有意な疼痛の緩和が認められた。

訳注

《実施組織》厚生労働省「「統合医療」に係る情報発信等推進事業」(eJIM:http://www.ejim.ncgg.go.jp/)[2016.8.9]
《注意》この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、eJIM事務局までご連絡ください。なお、2013年6月からコクラン・ライブラリーのNew review, Updated reviewとも日単位で更新されています。eJIMでは最新版の日本語訳を掲載するよう努めておりますが、タイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。

Plain language summary

Lifestyle interventions for treating acute gout attacks

This summary of a Cochrane review presents what we know from research about the effect of lifestyle modifications in the treatment of people with acute gout. There was one study included in this review, which looked at the benefits and safety of adding topical ice therapy to medications commonly used for treating acute gout (prednisolone and colchicine). Over a one week period, in addition to prednisolone and colchicine, ice was applied to the skin overlying the joints affected by acute gout, for half-an-hour, four times per day, to relieve symptoms of pain and warmth and to reduce signs of redness and swelling.

The review shows that in people with acute gout:

We are uncertain whether the reduction in pain seen with the addition of topical ice to standard treatment of prednisolone and colchicine, compared to prednisolone and colchicine alone, is a true effect because of the very low quality evidence.

Joint function, health-related quality of life, patient global assessment and side effects and complications were not reported.

We often do not have precise information about side effects and complications. Topical ice is likely to be a safe intervention.

What is gout and what are lifestyle interventions?

Gout is a very common cause of painful joint inflammation (arthritis) and is caused by urate crystals forming either within or around joints. The inflammation can lead to pain, redness, warmth and swelling of the affected joints, making the area difficult to touch or move. Some of the reasons why people get gout include their genetic make-up, being overweight, ingesting certain medications (for example cyclosporine), having impaired kidney function, and lifestyle habits such as drinking excessive amounts of alcohol and sugar-sweetened drinks.

Medications are the mainstay of acute gout treatment. Given the recognised association between certain lifestyle risk factors and gout development, lifestyle changes such as consuming more water, coffee, dairy milk and cherry juice, and having fewer sugar-sweetened drinks, alcoholic beverages, meat and seafood are commonly recommended to people with chronic gout to prevent recurrence of attacks.

Best estimate of what happens to people with acute gout using topical ice in addition to medications:

Joint pain (lower score means less pain)

People who used topical ice (for half-an-hour, four times per day for one week) in addition to medical treatment (oral prednisolone and colchicine) rated their pain 3.33 points lower on a 0 to 10 point pain scale (33% absolute improvement).
- People who used topical ice in addition to medical treatment (prednisolone and colchicine) rated their pain to be 2.25 points on a scale of 0 to 10.
- People who used medical treatment alone rated their pain to be 5.58 points on a scale of 0 to 10.

- Three people would need to be treated with topical ice for one person to benefit from pain relief.

Adverse events

Side effects or complications of using topical ice in addition to medical therapy were not reported in the study.

Résumé simplifié

Interventions axées sur le mode de vie pour les crises de goutte aiguë

Ce résumé d’une revue Cochrane représente l’état de nos connaissances découlant des recherches portant sur l’effet des modifications du mode de vie dans le traitement des personnes souffrant de crises de goutte aiguë. Une étude incluse dans cette revue a examiné les bénéfices et l'innocuité de l'ajout de glace topique aux médicaments couramment utilisés pour traiter les crises de goutte aiguë (le prednisolone et la colchicine). Pendant une période d’une semaine, en plus du prednisolone et de la colchicine, de la glace a été appliquée sur la peau recouvrant les articulations touchées par la goutte aiguë, pendant une demi-heure et quatre fois par jour, pour soulager les symptômes de la douleur et de la chaleur et réduire les signes de rougeur et les gonflements.

La revue montre que chez les personnes souffrant de crises de goutte aiguë:

Nous ne savons pas si la réduction de la douleur observée avec l'ajout de glace topique au traitement standard de prednisolone et de colchicine, par rapport au prednisolone et la colchicine seuls, indique un véritable effet en raison des preuves de très faible qualité.

La fonction articulaire, la qualité de vie, l'évaluation globale du patient, les effets secondaires et les complications n’étaient pas rapportés.

Nous ne disposons pas d'informations précises concernant les effets secondaires et les complications. La glace topique est susceptible d'être une intervention sûre.

Qu'est-ce que la goutte et que sont les interventions axées sur le mode de vie?

La goutte est une forme très courante d'inflammation articulaire douloureuse (arthrite) causée par des dépôts uratiques se formant soit au sein , soit autour, des articulations. L'inflammation peut provoquer une douleur, une rougeur et un gonflement des articulations affectées, rendant la partie sensible au toucher ou difficile à bouger. Certaines des raisons expliquant pourquoi des personnes souffrent de la goutte comprennent leur constitution génétique, leur état en surpoids, l'ingestion de certains médicaments (par exemple la cyclosporine), la présence de troubles de la fonction rénale et les habitudes de leur mode de vie, telles que la consommation excessive d'alcool et de boissons sucrées.

Les médicaments sont la base du traitement de la goutte aiguë. Étant donné l'association reconnue entre certains facteurs de risque liés au mode de vie et au développement de la goutte, des changements de mode de vie, tels qu’une plus grande consommation d'eau, de café, de produits laitiers et de jus de cerises et une baisse de la consommation de boissons sucrées, de boissons alcoolisées, de viande et de fruits de mer sont couramment recommandées aux personnes souffrant de goutte chronique pour prévenir la récurrence des crises.

Meilleure estimation de ce qui arrive aux personnes souffrant de goutte aiguë et utilisant de la glace topique en plus de médicaments :

La douleur articulaire (le score le plus bas signifie moins de douleur)

Les personnes ayant utilisé la glace topique (pendant une demi-heure, quatre fois par jour et sur une semaine) en supplément à un traitement médical (le prednisolone et la colchicine par voie orale) ont qualifié leur douleur de 3,33 points, sur une échelle de 0 à 10 points (amélioration absolue de 33%).
- Les personnes ayant utilisé de la glace topique en plus d’un traitement médical (le prednisolone et la colchicine) ont qualifié leur douleur comme étant de 2,25 points sur une échelle de 0 à 10.
- Les personnes ayant utilisé un traitement médical seul ont qualifié leur douleur comme étant de 5,58 points sur une échelle de 0 à 10.

- Trois personnes devraient être traitées avec de la glace topique pour qu’une personne puisse bénéficier d’un soulagement de la douleur.

Les effets indésirables

Les effets secondaires ou les complications suite à l'utilisation de la glace topique en plus du traitement médical n'étaient pas rapportés dans l'étude.

Notes de traduction

Traduit par: French Cochrane Centre 1st November, 2013
Traduction financée par: Financeurs pour le Canada : Instituts de Recherche en Santé du Canada, Ministère de la Santé et des Services Sociaux du Québec, Fonds de recherche du Québec-Santé et Institut National d'Excellence en Santé et en Services Sociaux; pour la France : Ministère en charge de la Santé

Resumo para leigos

Mudanças no estilo de vida no tratamento de crises de gota aguda

Este resumo da revisão Cochrane apresenta o que aprendemos a partir da pesquisa sobre o efeito da mudança do estilo de vida no tratamento de pessoas acometidas por gota aguda. Um estudo foi incluso nesta revisão, que demonstra os benefícios e a segurança em adicionar terapia com gelo local nas medicações comumente utilizadas no tratamento de gota aguda (prednisolona e colchicina). Após uma semana de duração, associados a prednisolona e colchicina, gelo foi aplicado à pele, aliviando as articulações acometidas pela gota aguda, durante quinze minutos, quatro vezes ao dia, para aliviar os sintomas de dor e calor e reduzir os sinais de vermelhidão e inchaço.

A revisão mostrou que nas pessoas com gota aguda:

Nós estamos incertos se a redução da dor observada com a utilização do gelo tópico para o tratamento padrão da prednisolona e colchicina, comparado ao uso de apenas prednisolona e colchicina, é um efeito real, devido à baixíssima qualidade das evidencias.

A função das articulações, qualidade de vida relacionada à saúde, avaliação completa do paciente e efeitos colaterais e complicações não foram reportadas.

Nós frequentemente não temos informações precisas sobre os efeitos colaterais e as complicações. É provável que gelo tópico seja uma intervenção segura.

O que é gota e o que são mudanças no estilo de vida?

Gota é uma causa muito comum de dor inflamatória articular (artrite) e é causada pela formação de cristais de urato quer dentro ou ao redor das articulações. A inflamação pode levar à dor, eritema, calor e inchaço nas articulações afetadas, dificultando a movimentação ou toque local. Algumas das razões do por que pessoas desenvolvem gota inclui o fator genético, sobrepeso, ingestão de medicações especificas (ciclosporina, por exemplo), tendo a função renal prejudicada, e hábitos de vida tais como o consumo excessivo de bebida alcoólica e bebidas adoçadas com açúcar.

Medicamentos são o pilar do tratamento da gota aguda. Dada a reconhecida associação entre certos fatores de risco do estilo de vida e desenvolvimento de gota, mudanças no estilo de vida tais como consumir mais água, café, leite de vaca e suco de cereja, e consumindo menos bebidas adoçadas com açúcar, bebidas alcoólicas, carne e frutos do mar são comumente recomendados para pessoas com gota crônica para prevenir crises recorrentes.

Melhor estimativa do que ocorre às pessoas com gota aguda utilizando gelo tópico associado aos medicamentos:

Dor articular (menor score significa menos dor)

Pessoas que usaram gelo tópico (quinze minutos, quatro vezes por dia durante 1 semana) associado ao tratamento medicamentoso (prednisolona oral e colchicina) avaliaram sua dor em 3.33 pontos a menos na escala de dor de 0 a 10 pontos (33% de melhora absoluta).
-Pessoas que utilizaram gelo tópico associado ao tratamento medicamentoso (prednisolona e colchicina) avaliaram sua dor em 2.25 pontos na escala de 0 a 10.
-Pessoas que usaram apenas o tratamento medicamentoso avaliaram sua dor em 5.58 pontos na escala de 0 a 10.

- Três pessoas deveriam ser tratadas com gelo tópico para uma pessoa se beneficiar no alivio da dor.

Eventos adversos

Efeitos colaterais ou complicações no uso de gelo tópico associado à terapia medicamentosa não foram reportados no estudo.

Notas de tradução

Traduzido por: Marcelo Zerbetto Fabricio, Unidade de Medicina Baseada em Evidências da Unesp, Brazil Contato: portuguese.ebm.unit@gmail.com

Laički sažetak

Promjene u načinu života za liječenje akutnog napadaja gihta

Ovaj sažetak Cochrane sustavnog pregleda prikazuje dokaze iz istraživanja o utjecaju promjena u načinu života na liječenje osoba s akutnim napadajem gihta. U ovaj pregled je uključena jedna studija, koja je ispitala djelotvornost i sigurnost dodavanja lokalne terapije ledom uz terapiju lijekovima koji se najčešće koriste za liječenje akutnog gihta (prednizolon i kolhicin). Tijekom jednog tjedna se, uz uzimanje prednizolona i kolhicina, led nanosio na kožu iznad zglobova pogođenih akutnim gihtom, pola sata, četiri puta dnevno, za ublažavanje simptoma boli i topline i kako bi smanjili crvenilo i otekline.

Dokazi pokazuju da u osoba s akutnim gihtom:

Zbog vrlo niske kvalitete dokaza nismo sigurni je li smanjenje boli koje vidimo kada dodamo led uz standardno liječenje prednisolonom i kolhicinom, u odnosu na samu terapiju lijekovima istinski učinkovito.

Podatci o funkciji zglobova, kvaliteti života vezanoj za zdravlje, pacijentova globalna procjena bolesti, kao ni nuspojave i komplikacije nisu prikazani.

Često nemamo precizne podatke o nuspojavama i komplikacijama. Stavljanje leda je vrlo vjerojatno siguran postupak.

Što je giht i što su intervencije u načinu života?

Giht je vrlo čest uzrok upale zglobova (artritisa), a uzrokovan je kristalima urata koji se stvaraju unutar ili oko zglobova. Upala može dovesti do boli, crvenila, topline i oteklina pogođenih zglobova, zbog čega je to područje bolno na dodir i teško pomično. Neki od razloga zašto ljudi dobivaju giht je genetska sklonost, prekomjerna tjelesna težina, konzumiranje određenih lijekova (npr. ciklosporin), oslabljena funkcija bubrega i loše životne navike, kao što je konzumacija velikih količine alkohola i zaslađenih napitaka.

Lijekovi su glavni način liječenja akutnog gihta. S obzirom na poznatu povezanost između pojedinih čimbenika rizika u načinu života i razvoja gihta, preporučuje se promjena životnih navika. Osobama oboljelima od kroničnog gihta obično se preporučuje konzumiranje većih količina vode, kave, mliječnih proizvoda i soka višnje, a što manje zaslađenih napitaka, alkoholnih pića, mesa i plodova mora kako bi se spriječilo ponavljanje napada.

Najbolji prikaz o tome što se događa s ljudima s akutnim gihtom koji koriste led uz lijekove:

Bol u zglobovima (niži broj znači manje boli)

Ljudi koji koriste led (pola sata, četiri puta dnevno tjedan dana) uz lijekove (prednizolon i kolhicin) ocijenili su svoju bol s 3,33 boda niže na ljestvici boli od 0 do 10 bodova (33% apsolutno poboljšanje).
- Ljudi koji koriste led uz lijekove (prednizolon i kolhicin) ocijenili su svoju bol sa 2,25 bodova na ljestvici od 0 do 10.
- Ljudi koji koriste samo lijekove ocijenili su bol s 5,58 bodova na ljestvici od 0 do 10.

- Tri osobe bi se morale liječiti ledom da bi se kod jedne osobe ublažila bol. Nuspojave Nuspojave ili komplikacije primjene leda uz terapiju lijekovima nisu opisane u studiji.

Nuspojave

Nuspojave ili komplikacije primjene leda uz terapiju lijekovima nisu opisane u studiji.

Bilješke prijevoda

Hrvatski Cochrane
Preveli: Mila Fabris i Marko Vrgoč
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr

平易な要約

急性痛風発作に対する生活習慣への介入効果

このコクラン・レビューの概要では、急性痛風発作の治療として生活習慣に介入した効果を対象とした研究から得られた情報を紹介する。本レビューの対象となったのは1件の試験で、急性の痛風発作治療に通常使用される薬剤(プレドニゾロンおよびコルヒチン)に加えて、局所冷却療法を実施する有益性および安全性を検討した。1週間にわたって、プレドニゾロンおよびコルヒチンの投与に加えて、急性痛風発作が起こった関節部分を覆っている皮膚を4回/日、30分間氷で冷却し、疼痛および熱感の症状を緩和し、発赤および腫脹の兆候を減らすよう試みた。

本レビューでは急性痛風について以下の結果が示された:

標準治療であるプレドニゾロンおよびコルヒチンに局所冷却療法を追加したところ、プレドニゾロンおよびコルヒチンの単独治療よりも疼痛を緩和させたが、エビデンスの質が極めて低いため、それが真の効果であるかどうかは不明である。

関節機能、健康関連のQOL、患者による全般的評価、副作用および合併症に関しては報告がなかった。

副作用や合併症について、多くの場合、詳細な情報を得ることができなかった。局所冷却療法は安全な介入であると思われる。

痛風とは何か。生活習慣への介入方法は。

痛風は、疼痛を伴う関節の炎症(関節炎)の原因として非常に多く認められ、関節の内側または周辺に尿酸結晶が形成されることによって起こる。炎症反応によって関節に疼痛、発赤、熱感および腫脹が起こり、その部分を触れたり動かしたりすることが困難になる。痛風が起こる原因として、特定の遺伝子構造、過体重、特定の薬剤の服用(シクロスポリンなど)、腎機能障害、アルコールや糖分の多い飲料の過剰摂取といった生活習慣などが挙げられる。

急性痛風の治療は、薬剤の使用が中心となっている。特定の生活習慣によるリスク要因が痛風の発症に関わっていることが広く知られている。そのため、慢性痛風患者における発作の再発を防ぐためには、水分、コーヒー、牛乳およびチェリージュースなどを十分に摂取し、糖分の多い飲料、アルコール飲料、肉および魚介類の摂取を控えるといった生活習慣の変化が一般的に推奨されている。

急性痛風発作を発症した患者において、薬剤治療に加えて局所冷却療法を実施した場合に予測される反応:

関節の疼痛(スコアの低下が疼痛緩和を示す)

薬剤治療(経口プレドニゾロンおよびコルヒチン)に加えて局所冷却療法(4回/日、30分間を一週間)を実施した患者では、疼痛に関して0~10点の疼痛評価スケールで3.33点の低下が認められた(33%の絶対的改善に相当)。
-薬剤治療(プレドニゾロンおよびコルヒチン)に加えて局所冷却療法を実施した患者では、疼痛の度合いは0~10点の評価スケールで2.25点であった。
-薬剤治療単独を実施した患者では、疼痛の度合いは10点評価スケール中5.58点であった。

-仮に3例に局所冷却療法による治療を受ける必要があった場合、うち1例が疼痛緩和の有益性を得られることになる。

有害事象

本試験では、薬剤治療に加えて局所冷却療法を実施した場合の副作用 または合併症は報告されていない。

訳注

《実施組織》厚生労働省「「統合医療」に係る情報発信等推進事業」(eJIM:http://www.ejim.ncgg.go.jp/)[2016.8.9]
《注意》この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、eJIM事務局までご連絡ください。なお、2013年6月からコクラン・ライブラリーのNew review, Updated reviewとも日単位で更新されています。eJIMでは最新版の日本語訳を掲載するよう努めておりますが、タイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。

Summary of findings(Explanation)

Summary of findings for the main comparison. Lifestyle interventions for acute gout
  1. 1 Trial did not adequately conceal treatment allocation; blind study participants, personnel, outcome assessors
    2 Small sample size
    3 Number needed to treat to benefit (NNTB) not applicable when result is non-statistically significant. NNT for continuous outcomes calculated using the Wells calculator software available from the Cochrane Musculoskeletal Group editorial office

Lifestyle interventions for acute gout
Patient or population: patients with acute gout
Settings: hospital inpatient and outpatient clinic
Intervention: lifestyle intervention
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments
Assumed riskCorresponding risk
Control Lifestyle intervention
Pain reduction
10 cm VAS. Scale from: 0 to 10 cm (0 is no pain).
Follow-up: 1 week
The mean pain reduction in the control group was
4.42 cm on a 10 cm visual analogue scale
The mean pain reduction in the intervention group was
3.33 cm greater
(5.84 to 0.82 greater)
 19
(1 study)
⊕⊕⊝⊝
low 1,2
Absolute risk difference: 33% less pain with topical ice (95% CI -58% to -8%). Relative percentage change: -75% (95% CI -132% to -19%). NNT = 3
Number of participant withdrawals due to adverse events - not measuredSee commentSee commentNot estimable-See commentNot measured
Reduction of joint inflammation
Tape measure - joint circumference (cm)
Follow-up: 1 week
The mean reduction of joint inflammation in the control groups was
3.83 cm
The mean reduction of joint inflammation in the intervention groups was
2.07 cm higher
(1.56 lower to 5.7 higher)
 19
(1 study)
⊕⊕⊝⊝
low 1,2
NNT not calculated, non-statistically significant3
Joint function - not measuredSee commentSee commentNot estimable-See commentNot measured
Health-related quality of life - not measuredSee commentSee commentNot estimable-See commentNot measured
Patient global assessment - not measuredSee commentSee commentNot estimable-See commentNot measured
Serious adverse events - not measuredSee commentSee commentNot estimable-See commentNot measured
*The basis for the assumed risk (e.g., the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval
GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Background

Description of the condition

Gout is a potentially progressive and debilitating form of chronic inflammatory arthritis that is caused by deposition of monosodium urate crystals in synovial fluid and other tissues (Neogi 2011). It affects 1% to 2% of adults in developed countries (Richette 2010) and can have a significant adverse impact upon a person's quality of life. People who suffer from recurrent attacks frequently experience pain and disability, reduced health-related quality of life (HRQoL), reduced productivity and increased morbidity (Singh 2011a). Both its incidence and prevalence have appeared to rise in recent decades (Choi 2005a; Richette 2010). The reasons behind this are probably multi-factorial and potentially related to increasing longevity, rising rates of obesity and the metabolic syndrome, and shifts in dietary habits and lifestyle (Choi 2005a; Choi 2005b; Neogi 2011; Richette 2010).

Hyperuricaemia, which is defined as a serum urate level ≥ 0.404 mmol/l or 6.8 mg/dL (the saturation point of urate in biological fluids based on in vitro studies), is the key predisposing factor for gout development (Neogi 2011; Schumacher 2008). Factors such as chronic hyperuricaemia, joint trauma or irritation (for example the first metatarsophalangeal joint is a site of mechanical stress), cooler body temperature (for example at the helix of the ear and the foot) and joint disease (for example osteoarthritis) all promote monosodium urate (MSU) crystal deposition within joints and tophus formation. The process of acute gout is thought to begin with the abrupt release of MSU crystals into the joint space, triggered by factors such as metabolic changes (for example increases or decreases in serum urate level) and mechanical trauma. Inside the joint cavity, MSU crystals are phagocytosed by synovial lining cells, which leads to the formation of a complex known as the inflammasome. The inflammasome releases a variety of pro-inflammatory cytokines (for example interleukin-1, tumour necrosis factor α, interleukin-8) and chemokines, resulting in neutrophil influx into the synovial tissue and fluid and generation of an intense urate-induced inflammatory reaction (Schumacher 2008). An alternate pathway by which extracellular MSU crystals can activate monocytes is via toll-like receptors (TLR), TLR2 and TLR4 (expressed by macrophages), which induce interleukin-1 transcription. In vivo studies support the crucial role of interleukin-1β (IL-1β) and its pathway in MSU-induced inflammation, highlighting IL-1β blockade as a key therapeutic target for future gout trials (Richette 2010). Acute gout attacks typically resolve over a period of seven to 10 days without intervention (Neogi 2011). However, treatment with pharmacological agents such as non-steroidal anti-inflammatory drugs (NSAIDs) (Janssens 2008a), colchicine (Schlesinger 2006b), and possibly glucocorticoids (Janssens 2008b; Wechalekar 2013) and adrenocorticotropin hormone (ACTH) (Axelrod 1988; Mikadashi 1994) may facilitate more rapid onset of pain relief and minimisation of disability. Resting the inflamed joint and applying topical ice may also help (Neogi 2011; Richette 2010).

Lifestyle factors are another important contributing factor for the occurrence of acute gout attacks. Much of our current understanding of the lifestyle factors associated with gout is derived from large, cross-sectional, observational studies such as the Health Professionals Follow-up Study (HPFS) and the Third National Health and Nutrition Examination Survey (NHANES III) (Choi 2004c; Choi 2005b; Choi 2005c; Choi 2007b; Choi 2007c). The relationship between various lifestyle factors and gout can be summarised according to whether their association is regarded to increase the risk of, have no effect on, or decrease the risk of developing incident and recurrent gout. Lifestyle factors such as high dietary intake of purine-rich foods (particularly meat and seafood), ethanol (particularly beer and spirits), fructose-sweetened drinks and sweet fruits (apples, oranges), and weight gain and obesity are recognised risk factors for gout development (Choi 2004a; Choi 2004b; Choi 2010b; Neogi 2011; Singh 2011b). On the contrary, protein and purine-rich vegetable intake is regarded as having no effect on gout risk, having been vindicated as risk factors for gout, while ingestion of dairy products (low fat or skim milk), decaffeinated coffee, vitamin C and weight loss are considered to exert a protective effect against gout development (Choi 2010b; Neogi 2011; Richette 2010). For these reasons, lifestyle modifications are commonly recommended in combination with urate lowering medications for helping to reduce the risk of gout recurrence and chronic arthropathy developing in the long term (Neogi 2011; Richette 2010). However, the role of lifestyle interventions for treating acute gout attacks is less well established. Given that rapid reduction in serum urate levels is a recognised trigger for acute gouty arthritis (Richette 2012; Schumacher 2008), aggressive implementation of lifestyle interventions, such as those used in chronic gout treatment, may have an undesirable short-term effect of increasing the risk of gout flares. Therefore evaluation of the trial data, particularly in relation to the potential harm as well as benefits associated with using lifestyle interventions for treating acute gout attacks, is warranted.

Description of the intervention

Lifestyle interventions that may help in treating acute gout include resting the affected joint or joints and applying topical ice. Interventions employed in chronic gout for reducing gout attack frequency, such as maintaining adequate hydration, increasing coffee, dairy and cherry intake, and reducing dietary consumption of fructose-sweetened drinks, alcoholic beverages, meat and seafood (Richette 2010), will also be examined.

How the intervention might work

A mechanism by which reducing purine intake may help decrease acute gout attacks relates to free fatty acids (FFAs). The mere presence of monosodium urate (MSU) crystals in synovial fluid has been shown to be insufficient for triggering gout attacks and a 'second signal' appears to be necessary (Giamarellos-Bourboulis 2009; Joosten 2010; Richette 2012). A potential candidate is high levels of serum FFAs, which are increased following ingestion of purine-rich foods and alcohol. In the presence of FFAs, MSU crystals induce the production and release of IL-1β, a pro-inflammatory cytokine which is considered responsible for initiating clinical inflammation (Richette 2012). Therefore, reducing consumption of purine-rich foods and alcohol may facilitate the removal of the inciting agent required for initiating and sustaining acute gout attacks.

The ingestion of milk proteins (casein, lactalbumin, orotic acid) has been shown to exert a uricosuric effect in healthy people (Dalbeth 2010). Furthermore, in experimental models of acute gout, certain dairy fractions such as glycomacropeptide and G600 milk fat extract have been demonstrated to have anti-inflammatory effects (Dalbeth 2012), which may help with resolution of the acute inflammation seen with gout attacks.

Cherry consumption has been demonstrated to have a urate lowering effect. Cherry products contain high levels of anthocyanins, which have anti-inflammatory properties that may help alleviate the pain and inflammation associated with gout attacks (Zhang 2012).

Adequate hydration is important for helping maintain the solubility of urate in joint fluid and avoiding intra-articular dehydration and subsequent increases in joint fluid urate concentration, supersaturation and crystal formation (Choi 2005a).

The topical application of ice has been demonstrated to exert an anaesthetic effect in acutely inflamed joints (Schlesinger 2006a). In animal models of gouty arthritis, cooling joints has also been shown to reduce intra-articular temperatures, hyperaemia, cellular infiltration and crystal-induced inflammation and synovitis (Schlesinger 2006a).

Why it is important to do this review

Lifestyle interventions are commonly recommended in the management of chronic gout due to their urate lowering effects. However, the role of lifestyle interventions as an adjunct to medications for treating acute gout attacks is not well established. Indeed, there may be theoretical concerns that applying lifestyle interventions, which effect urate lowering, during the acute setting may cause harm. Therefore, a systematic review of the evidence from clinical trials on the safety and efficacy of lifestyle interventions for treating acute gout attacks (which has not previously been undertaken) is warranted. The results of the review are likely to be important for informing clinical practice and determining whether further research is required to establish the value of lifestyle interventions for acute gout.

Objectives

The objective of this systematic review was to evaluate the benefits and safety of lifestyle interventions for the treatment of people with acute gout.

Methods

Criteria for considering studies for this review

Types of studies

All published randomised or quasi-randomised controlled trials which compared one or more lifestyle interventions to another therapy (active or placebo, pharmacological or non-pharmacological interventions) for treating acute gout were considered for inclusion. Only trials that were published as full articles or were available as a full trial report were included.

Types of participants

Adult patients (aged 18 years or older) diagnosed with acute gout, either via joint arthrocentesis with identification of uric acid crystals or according to the author's description. Populations that included a mix of people with acute gout and other musculoskeletal pain were excluded unless results for the acute gout population could be separated out from the analysis.

Types of interventions

All trials that evaluated one or a combination of lifestyle interventions for acute gout were eligible for inclusion. This included trials on smoking cessation, resting the affected joints, increasing intake of coffee, dairy milk or water, and reducing dietary intake of fructose-sweetened drinks, ethanol (particularly beer and spirits) and purine-rich foods (particularly meat and seafood). Trials that evaluated one or a combination of lifestyle interventions for chronic gout were excluded as these have been the subject of another Cochrane review (Moi 2013).

Comparators could be:

  1. placebo;

  2. no treatment;

  3. one lifestyle intervention versus another lifestyle intervention;

  4. paracetamol;

  5. non-steroidal anti-inflammatory drugs (NSAIDs);

  6. colchicine;

  7. glucocorticoids (intra-articular, systemic);

  8. interleukin-1 (IL-1) inhibitors;

  9. combination therapy (combinations of any of the above).

Types of outcome measures

We included the outcome measures for use in clinical trials of acute gout that have been proposed by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) network (Grainger 2009).

Main outcomes
  1. Benefits: participant-reported pain reduction in the target joint(s) affected by acute gout, e.g., measured on a visual analogue scale (VAS) or numerical rating scale such as the five-point Likert scale, or reported as pain relief of 50% or greater.

  2. Safety: number of study participant withdrawals due to adverse events (AEs).

Other outcomes
  1. Reduction of joint inflammation (joint swelling, erythema, temperature), e.g., measured using a VAS or numerical rating scale

  2. Function of the target joint

  3. Health-related quality of life (HRQoL) as measured by generic instruments (such as the Medical Outcomes Study Short-Form-36 Survey (SF-36))

  4. Patient global assessment, e.g., as measured on the Patient's Global Assessment of Response to Treatment (PGART)

  5. Proportion of participants with serious adverse events (SAEs), defined as AEs that are fatal, life-threatening or require hospitalisation

For the purpose of this review, if feasible, we planned to group the outcomes into short-term (up to two weeks), medium-term (two to six weeks) and long-term (more than six weeks) outcomes.

Search methods for identification of studies

Electronic searches

We searched the following databases for randomised controlled trials (RCTs) or quasi-randomised clinical controlled trials (CCTs) using the search strategies detailed in the appendices:

  1. Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 4) (Appendix 1);

  2. MEDLINE Ovid (1948 to week 3 March 2013) (Appendix 2);

  3. EMBASE (1980 to Week 13, 2013) (Appendix 3).

We did not apply any language restrictions.

Searching other resources

We searched the American College of Rheumatology (ACR) and EUropean League Against Rheumatism (EULAR) conference abstracts from 2010 and 2011. We handsearched the reference lists of included articles and relevant reviews to identify any additional studies not retrieved by the aforementioned search strategy.

Data collection and analysis

Selection of studies

Two review authors (JM, MS) independently assessed all retrieved trials to identify those that fulfilled the criteria for inclusion in this systematic review. We retrieved all relevant articles in full text for closer examination. Disagreement about study inclusion or exclusion was resolved by consensus or by discussion with a third author (RB) if needed. Studies were translated into English where necessary.

Data extraction and management

Two authors (JM, MS) independently extracted the following relevant information from included trials using a predefined data extraction form: study design, characteristics of the study population (age, gender, presence or absence of concurrent urate lowering medication use or tophi), lifestyle interventions, control interventions, outcome measures (mean and standard deviation for continuous outcomes, number of events and participants for dichotomous outcomes), timing of outcome assessment, and methodological domains relevant to 'Risk of bias' assessment. We resolved differences in data extraction by referring back to the original articles and establishing consensus. A third author (RB) was consulted to help resolve differences if necessary.

Assessment of risk of bias in included studies

We assessed the potential for bias in the included studies using the Cochrane Collaboration's tool for assessing risk of bias (Higgins 2011). Two review authors (JM, MS) independently assessed the risk of bias in included trials and resolved any disagreements by consensus or consultation with a third author (RB) if necessary. We assessed the following methodological domains:

  1. random sequence generation, to determine if the method of generating the randomisation sequence was adequate to prevent biased allocation to interventions;

  2. allocation concealment, to determine if adequate methods were used to conceal allocation to interventions;

  3. blinding of participants, personnel and outcome assessors for each outcome measure, to determine if adequate methods to prevent knowledge of the allocated interventions by study participants, personnel and outcome assessors occurred during the study;

  4. incomplete outcome data;

  5. selective outcome reporting; and

  6. other potential sources of bias.

To determine the risk of bias of an included study, for each criterion we evaluated the presence of sufficient information and the likelihood of potential bias. We rated each of these criteria either as 'low risk', 'high risk' or 'unclear risk' (either lack of information or uncertainty over the potential for bias).

Measures of treatment effect

We planned to summarise the data in a meta-analysis only if there was sufficient clinical and statistical homogeneity. For continuous data, we analysed results as mean differences (MD) between the intervention and comparator groups, with corresponding 95% confidence intervals (CI). The MD between treated group and control group was weighted by the inverse of the variance in the pooled treatment estimate. However, when different scales were used to measure the same conceptual outcome (for example, function or pain), we calculated standardised mean differences (SMDs) instead, with corresponding 95% CIs. SMDs were calculated by dividing the MD by the standard deviation, resulting in a unitless measure of treatment effect. For dichotomous data, we calculated a risk ratio (RR) with corresponding 95% CI.

Unit of analysis issues

For studies containing more than two intervention groups, making multiple pair-wise comparisons between all possible pairs of intervention groups possible, we planned to include the same group of participants only once in the meta-analysis. In the event that cross-over trials were identified in which the reporting of continuous outcome data precluded paired analysis, these data were not included in a meta-analysis in order to avoid unit of analysis errors. Where carry-over effects were thought to exist, and where sufficient data existed, data from the first period only were included in the analysis (Higgins 2011). We planned to extract data from all time points and combine them into short-term (up to two weeks), medium-term (over two weeks to six weeks) and long-term (more than six weeks) outcomes, though this depended on the feasibility of doing so from the available data. If more than one time point was reported within the subgroup (for example, at one week and two week follow-up), we extracted the last outcome.

Dealing with missing data

Where data were missing or incomplete, we sought further information from the study authors. In cases where individuals were missing from the reported results and no further information was forthcoming from the study authors, we assumed the missing values to have a poor outcome.

For dichotomous outcomes that measured adverse events (for example, number of withdrawals due to adverse events) the withdrawal rate was calculated using the number of patients that received treatment as the denominator (worst-case analysis). For dichotomous outcomes that measure benefits (for example, patient-reported reduction in joint pain during acute gout) we calculated the worst-case analysis using the number of randomised participants as the denominator.

For continuous outcomes (for example, pain) we calculated the MD or SMD based on the number of patients analysed at the time point. If the number of patients analysed was not presented for each time point, we used the number of randomised patients in each group at baseline. Where possible, we computed missing standard deviations from other statistics such as standard errors, CIs or P values according to the methods recommended in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). If standard deviations were not able to be calculated, we planned to impute them (for example, from other studies in the meta-analysis (Higgins 2011)).

Assessment of heterogeneity

Prior to meta-analysis, we planned to assess studies for clinical homogeneity with respect to type of therapy, control group and the outcomes. For any studies judged as clinically homogeneous, we planned to estimate statistical heterogeneity using the I2 statistic (Deeks 2011), using the following as a rough guide for interpretation: 0% to 40% might not be important, 30% to 60% may represent moderate heterogeneity, 50% to 90% may represent substantial heterogeneity and 75% to 100% considerable heterogeneity. In cases of considerable heterogeneity (defined as I2 ≥ 75%), we planned to explore the data further, including subgroup analysis, in an attempt to explain the heterogeneity.

Assessment of reporting biases

In order to determine whether reporting bias was present, we determined whether the protocol for the RCT was published before recruitment of patients to the study was started. For studies published after 1 July 2005, we screened the Clinical Trial Register at the International Clinical Trials Registry Platform of the World Health Organization (http://apps.who.int/trialsearch/) (DeAngelis 2004).

We evaluated whether selective reporting of outcomes was present (outcome reporting bias).

We compared the fixed-effect model estimate against the random-effects model to assess the possible presence of small sample bias in the published literature (that is, in which the intervention effect is more beneficial in smaller studies). In the presence of small sample bias, the random-effects model estimate of the intervention is more beneficial than the fixed-effect model estimate (Sterne 2011). We planned to further explore the potential for reporting bias using funnel plots, if more than 10 studies were included.

Data synthesis

Where studies were sufficiently homogeneous that it remained clinically meaningful for them to be pooled, we planned to perform meta-analysis using a random-effects model, regardless of the I2 results. We planned to perform analyses using the Cochrane Collaboration's statistical software, Review Manager 2011, and produce forest plots.

Subgroup analysis and investigation of heterogeneity

Where sufficient data were available, the following subgroup analysis was planned:

1. polyarticular versus monoarticular and oligoarticular gout attacks.

Sensitivity analysis

Where sufficient studies existed, sensitivity analyses were planned to assess the impact of any bias attributable to inadequate or unclear treatment allocation (including studies with quasi-randomised designs) and inadequate blinding of study participants, personnel and outcome assessors.

Presentation of key results

We produced a 'Summary of findings' table to illustrate key information concerning the quality of evidence, the magnitude of effect of the interventions examined, and the sum of available data on the most important patient-relevant outcomes as recommended by The Cochrane Collaboration (Schünemann 2011a).

The 'Summary of findings' table included an overall grading of the evidence related to each of the main outcomes using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach (Schünemann 2011b). In addition to the absolute and relative magnitude of effect provided in the 'Summary of findings' table, for dichotomous outcomes we calculated the number needed to treat to benefit (NNTB) or the number needed to treat to harm (NNTH) from the control group event rate (unless the population event rate was known) and the risk ratio using the 'Visual Rx' programme (Cates 2008). For continuous outcomes, we calculated the NNT using the Wells calculator software, available at the Cochrane Musculoskeletal Group editorial office (http://musculoskeletal.cochrane.org/). We determined the minimal clinically important difference (MCID) for each outcome for input into the calculator.

We presented the following outcomes (at the latest time point) in a 'Summary of findings' table (Schünemann 2011a; Schünemann 2011b):

  1. participant-reported pain reduction in the target joint(s);

  2. reduction of inflammation;

  3. function of the target joint;

  4. HRQoL;

  5. patient global assessment;

  6. number of study participant withdrawals due to AEs;

  7. proportion of participants with SAEs.

Results

Description of studies

Results of the search

The search strategy yielded 808 references (see Figure 1). After excluding 114 duplicate references, 277 references that were not RCTs or CCTs, 364 non-gout related references, and 50 references with no or incorrect interventions, we retrieved three articles for full assessment. Only one study published in English was found to meet our inclusion criteria (Schlesinger 2002). Two other trials were published in Mandarin and are awaiting translation and classification (Zeng 2012; Zhao 2009) (see Characteristics of studies awaiting classification). The review will be updated to include data from these studies if they are found to meet the inclusion criteria.

Figure 1.

Study flow diagram.

Included studies

Details of the included trial are provided in the table 'Characteristics of included studies'. This RCT was performed in the USA, was of parallel group design, included 19 participants, and was of one week's duration (Schlesinger 2002).

Study participants

Schlesinger 2002 included participants with gout, proven through arthrocentesis and isolation of monosodium urate (MSU) crystals in the synovial fluid. Participants were recruited during the acute phase of a gouty arthritis attack and stable background allopurinol therapy was continued during the trial. No other demographic information on study participants was provided, despite contacting the trial author.

Interventions

Schlesinger 2002 compared the addition of topical ice therapy (applied for 30 minutes, four times per day) to the combination of oral prednisolone (30 mg/day x 2 days, 20 mg/day x 2 days, 10 mg/day x 2 days) and colchicine (0.6 mg/day) against an identical medication regimen without topical ice therapy, over six days.

Timing of follow-up

Schlesinger 2002 reported outcomes at a single time point, one week following topical ice intervention.

Outcome assessment

Schlesinger 2002 reported two of the five essential outcome domains proposed by the OMERACT network for use in studies of acute gout (Schumacher 2009). These study endpoints included a reduction in joint pain (measured using a 10 cm VAS) and swelling (recorded as the circumference of gout affected joints, using a tape measure, expressed in centimetres).

Schlesinger 2002 also reported laboratory values for serum uric acid (SUA), erythrocyte sedimentation rate (ESR) and synovial fluid analysis (leukocyte count, fluid volume) pre- and post-intervention with topical ice. The number and types of AEs and SAEs were not reported.

Excluded studies

No studies were excluded after review of the full texts of potentially eligible articles.

Risk of bias in included studies

The results of the risk of bias assessment are presented in Figure 2. The included trial failed to meet all of the criteria for low risk of bias and the results may therefore be biased.

Figure 2.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

Schlesinger 2002 adequately described their method of sequence generation but their method of allocation concealment ("folded paper note") was assessed to be insufficient for blinding investigators to treatment allocation and was deemed high risk of bias.

Blinding

It was unclear whether Schlesinger 2002 blinded participants, personnel, or outcome assessors. Due to the nature of the intervention (topical ice therapy) it would be difficult to blind participants.

Incomplete outcome data

Schlesinger 2002 reported that there were no study participant withdrawals and provided the outcome data for all randomised participants.

Selective reporting

Schlesinger 2002 reported the data for all pre-specified efficacy outcomes.

Other potential sources of bias

No other potential sources of bias were identified.

Effects of interventions

See: Summary of findings for the main comparison Lifestyle interventions for acute gout

See: Summary of findings for the main comparison for the main comparison.

Topical ice therapy plus prednisolone and colchicine versus prednisolone and colchicine

Data from one unblinded trial of acute gout (19 participants) (Schlesinger 2002) showed that the pain from an attack of acute gouty arthritis was significantly improved from baseline when topical ice therapy was added as an adjunct to oral prednisolone tapered over six days (30 mg x 2 days, 20 mg x 2 days, 10 mg x 2 days) and colchicine 0.6 mg/day x 6 days) (MD -3.33 cm, 95% CI -5.84 to -0.82) (Analysis 1.1; Figure 3).

Figure 3.

Forest plot of comparison: medical treament (prednisolone and colchicine) versus topical ice plus medical treatment. Outcome 1.1: ice versus no ice: mean pain reduction (10 cm VAS) after one week.

No statistical difference was identified in the results between the two groups when comparing mean reduction of joint swelling (MD 2.07 cm, 95% CI -1.56 to 5.70) (Analysis 1.2; Figure 4).

Figure 4.

Forest plot of comparison: medical treament (prednisolone and colchicine) versus topical ice plus medical treatment. Outcome 1.2: ice versus no ice: mean reduction in joint swelling (circumference in centimeters) after one week.

Other outcomes that were not included in this review but were reported in Schlesinger 2002 were the following. There were no between-group differences in synovial fluid analysis in terms of mean reductions in synovial fluid leukocyte count (MD 71/mm3, 95% CI -9565 to 9707) or synovial fluid volume (MD 16.08 mL, 95% CI -6.45 to 38.61) (data not shown).

Discussion

Summary of main results

One unblinded trial of 19 participants, at high risk of bias, found that there was a significant difference in improvement in pain at one week (3.33 points greater improvement on a 10 cm VAS) when topical ice was used as an adjunct to a combination of oral prednisolone and colchicine. No significant between-group differences were identified in terms of improvement in joint swelling at one week. Information about AEs or SAEs were not reported.

Overall completeness and applicability of evidence

There was a notable lack of trial data to support commonly prescribed lifestyle interventions used in acute gout treatment. Despite evidence from cross-sectional observational studies of a harmful association between the consumption of alcohol (beer, liquor), fructose-sweetened soft drinks, sweet fruits (apples, oranges), meat, seafood (oily fish, shellfish) and gout development (Choi 2010a; Choi 2010b), the reported protective effects of ingesting water, dairy milk, coffee, cherries, vitamin C for preventing gout recurrence (Choi 2004a; Choi 2005a; Choi 2007a; Dalbeth 2010; Zhang 2012), and the assumed analgesic benefits of resting inflamed joints during an acute attack of gouty arthritis, there was no trial evidence to support these observations.

Quality of the evidence

We judged the evidence on lifestyle interventions for acute gout treatment as low quality, according to the GRADE assessment, since it was based on a single small trial, which met the criteria for high or unclear risk of bias in five out of seven domains of bias assessment, including lack of blinding of participants and study assessors, and reporting bias. We suspect that the small number of trials identified is likely to be a reflection of a lack of high quality research in the area rather than publication bias.

Potential biases in the review process

We are confident that the broad literature search used in this review has captured relevant literature and minimised the likelihood that we missed any relevant trials. In the event of incomplete or unclear reporting of trial data, the trial authors were contacted by the review authors to obtain pertinent unpublished data or clarification of results was sought, respectively. In the case of eligible trials being published in languages other than English, translation of trials was requested. Trial selection, data extraction, and risk of bias assessment were undertaken independently by two authors to minimise bias.

Agreements and disagreements with other studies or reviews

The findings of our review are consistent with the conclusions of the recently updated 2012 American College of Rheumatology (ACR) guidelines for management of gout (Khanna 2012). In addition to recommendations to institute prompt pharmacological treatment for acute gout, providing instructions for managing recurrence, and providing patient education on lifestyle, dietary and other triggers of acute attacks, the authors also advocated topical ice application as an appropriate adjunctive measure to one or more pharmacologic therapies for acute gouty arthritis. In a separate cochrane review of lifestyle interventions for the treatment of chronic gout, a single trial, at moderate risk of bias, showed that skim milk enriched with the dairy fractions glycomacropeptide and G600 provided no additional benefit over standard skim milk or lactose powder in reducing the frequency of gout flares (Moi 2013).

Authors' conclusions

Implications for practice

While there is good evidence from observational studies of an association between various lifestyle risk factors and development of gout, there is a paucity of high quality evidence to either support or refute the use of lifestyle interventions for treatment of acute gout. While based upon very low quality evidence, one week of topical ice may be a useful adjunct to medical treatment for managing oligoarticular attacks of acute gout, and is likely to be safe.

Implications for research

Randomised controlled trials assessing lifestyle interventions to treat acute gout are needed before any conclusions can be made about the role of lifestyle interventions for reducing the symptoms of acute gout.

Planned trials should consider inclusion of the proposed set of outcomes proposed by OMERACT for studies of acute gout, including reduction in target joint pain, swelling, tenderness, patient global assessment, physician global assessment and functional disability (Schumacher 2009). The CONSORT statement should also be used as a guide for both designing and reporting trials (Boutron 2008).

Trial reporting should include the methods of randomisation and treatment allocation concealment; blinding of study participants, study personnel and outcome assessment; follow-up of all participants who entered the trial; and complete reporting of outcomes. Sample sizes should be reported and have adequate power to answer the research question; ideally trials should assess both the benefits and risks of lifestyle interventions. To enable the comparison and pooling of the results of randomised controlled trials, we suggest that future trials report means with standard deviations for continuous measures or number of events and total numbers analysed for dichotomous measures, and use standardised measurement tools for reporting relevant outcomes.

Acknowledgements

The authors thank Louise Falzon, former Trials Search Co-ordinator of the Cochrane Musculoskeletal Group, for designing the search strategy.

Data and analyses

Download statistical data

Comparison 1. Medical treament (prednisolone and colchicine) versus topical ice plus medical treatment
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Ice vs. no Ice: mean pain reduction (10cm VAS) after one week1 Mean Difference (IV, Random, 95% CI)Subtotals only
2 Ice vs. No Ice: mean reduction in joint swelling (circumference in centimeters) after one week1 Mean Difference (IV, Random, 95% CI)Subtotals only
Analysis 1.1.

Comparison 1 Medical treament (prednisolone and colchicine) versus topical ice plus medical treatment, Outcome 1 Ice vs. no Ice: mean pain reduction (10cm VAS) after one week.

Analysis 1.2.

Comparison 1 Medical treament (prednisolone and colchicine) versus topical ice plus medical treatment, Outcome 2 Ice vs. No Ice: mean reduction in joint swelling (circumference in centimeters) after one week.

Appendices

Appendix 1. CENTRAL search strategy

#1 MeSH descriptor Gout explode all trees

#2 gout*:ti,ab

#3 (#1 OR #2)

#4 MeSH descriptor Ethanol explode all trees

#5 ethanol:ti,ab

#6 MeSH descriptor Alcohol-Related Disorders explode all trees

#7 MeSH descriptor Alcohol Drinking, this term only

#8 alcohol*:ti,ab

#9 MeSH descriptor Exercise explode all trees

#10 MeSH descriptor Exercise Therapy explode all trees

#11 MeSH descriptor Exercise Movement Techniques explode all trees

#12 MeSH descriptor Physical Education and Training explode all trees

#13 MeSH descriptor Physical Fitness, this term only

#14 MeSH descriptor Physical Exertion, this term only

#15 MeSH descriptor Sports explode all trees

#16 exercis*:ti,ab

#17 sport*:ti,ab

#18 (physical* next (fit* or exert* or activ*)):ti,ab

#19 (run* or jog* or walk*):ti,ab

#20 (swim* or cycl* or bicycl*):ti,ab

#21 train*:ti,ab

#22 kinesi?therap*:ti,ab

#23 ((weight or muscle*) next (strength* or resistance)):ti,ab

#24 endurance:ti,ab

#25 MeSH descriptor Tobacco explode all trees

#26 MeSH descriptor Tobacco Use Disorder, this term only

#27 MeSH descriptor Tobacco Use Cessation explode all trees

#28 MeSH descriptor Tobacco Smoke Pollution explode all trees

#29 MeSH descriptor Nicotine, this term only

#30 smok*:ti,ab

#31 (cigarette* or cigar* or pipe*):ti,ab

#32 (#4 OR #5 OR #6 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31)

#33 MeSH descriptor Weight Loss explode all trees

#34 weight loss:ti,ab

#35 (weight near/2 (lo* or reduc* or eliminat*)):ti,ab

#36 ((body mass index or bmi) near/3 (los* or reduc* or decreas* or low*)):ti,ab

#37 (Waist circumference near/2 (reduc* or low* or small*)):ti,ab

#38 (Waist size near/2 (reduc* or low* or small*)):ti,ab

#39 energy next restrict*:ti,ab

#40 (calor* near/2 (restrict* or reduc* or low*)):ti,ab

#41 MeSH descriptor Anti-Obesity Agents explode all trees

#42 (appetite near/2 suppress*):ti,ab

#43 orlistat:ti,ab

#44 xenical:ti,ab

#45 alli@ti,ab

#46 tetrahydrolipstatin:ti,ab

#47 phentermine:ti,ab

#48 phenyl-tertiary-butylamine:ti,ab

#49 Ionamin:ti,ab

#50 adipex-P:ti,ab

#51 anoxine-AM:ti,ab

#52 duromine:ti,ab

#53 metermine:ti,ab

#54 mirapront:ti,ab

#55 obephen:ti,ab

#56 obestin-30:ti,ab

#57 phentremene:ti,ab

#58 phentrol:ti,ab

#59 phenterex:ti,ab

#60 phentromin:ti,ab

#61 "pro-fast SA":ti,ab

#62 redusa:ti,ab

#63 panbesy:ti,ab

#64 "phentermine trenker":ti,ab

#65 Obenix:ti,ab

#66 Oby-trim:ti,ab

#67 Teramine:ti,ab

#68 Zantryl:ti,ab

#69 Sinpet:ti,ab

#70 Supremin:ti,ab

#71 Umine:ti,ab

#72 Weltmine:ti,ab

#73 Aplenzin:ti,ab

#74 (#33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46 OR #47 OR #48 OR #49 OR #50 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56 OR #57 OR #58 OR #59 OR #60 OR #61 OR #62 OR #63 OR #64 OR #65 OR #66 OR #69 OR #70 OR #71 OR #72 OR #73)

#75 MeSH descriptor Diet explode all trees

#76 diet*:ti,ab

#77 MeSH descriptor Nutrition Therapy explode all trees

#78 (lacto-vegetarian* or lacto vegetarian* or vegetarian* or non-vegetarian*):ti,ab

#79 non near/2 vegetarian*:ti,ab

#80 vegan*:ti,ab

#81 (Cretan or Mediterranean):ti,ab

#82 MeSH descriptor Fasting, this term only

#83 fast*:ti,ab

#84 (protein near/2 (restrict* or reduc* or low* or elim*)):ti,ab

#85 (purine near/2 (restrict* or reduc* or low* or elim*)):ti,ab

#86 (fat near/2 (restrict* or reduc* or low* or elim)):ti,ab

#87 (triglyceride near/2 (restrict* or reduc* or low* or elim*)):ti,ab

#88 (cholesterol near/2 (restrict* or reduc* or low* or elim*)):ti,ab

#89 (diet near/3 (reduc* or low* or restrict* or elim*)):ti,ab

#90 (#75 OR #76 OR #77 OR #78 OR #78 OR #79 OR #80 OR #81 OR #82 OR #83 OR #84 OR #85 OR #86 OR #87 OR #88 OR #89)

#91 MeSH descriptor Dairy Products explode all trees

#92 (milk or cheese* or yog?urt or dairy):ti,ab

#93 MeSH descriptor Milk, this term only

#94 MeSH descriptor Cultured Milk Products, this term only

#95 (#91 OR #92 OR #93 OR #94)

#96 MeSH descriptor Sucrose explode all trees

#97 MeSH descriptor Fructose, this term only

#98 (sucrose* or lactose* or glucose* or fructose* or glycerine* or lycerine* or dextrose* or aspartame* or polycose* or sacchar* or sugar*):ti,ab

#99 (sweet* near/6 (solution* or tast*)):ti,ab

#100 (Diet* near/3 (drink* or beverage*)):ti,ab

#101 (soft near/2 (drink* or beverage*)):ti,ab

#102 (soda or sodas):ti,ab

#103 (#96 OR #97 OR #98 OR 99 OR #100 OR #101 OR #102)

#104 MeSH descriptor Coffee, this term only

#105 MeSH descriptor Caffeine, this term only

#106 (coffee or caffiene or caffeinated or decaffeinated):ti,ab

#107 (#104 OR #105 OR #106)

#108 MeSH descriptor Life Style explode all trees

#109 (life near/2 (style* or change$*or event*)):ti,ab

#110 lifestyle*:ti,ab

#111 MeSH descriptor Social Support, this term only

#112 "social support":ti,ab

#113 MeSH descriptor Relaxation explode all trees

#114 MeSH descriptor Relaxation Therapy, this term only

#115 relax*:ti,ab

#116 MeSH descriptor Self Efficacy, this term only

#117 (self next (efficac* or help or manag* or care)):ti,ab

#118 MeSH descriptor Health Promotion explode all trees

#119 MeSH descriptor Health Education explode all trees

#120 (health next (promot* or educat*)):ti,ab

#121 (motivat* next (therap* or interview*)):ti,ab

#122 (#108 OR #109 OR #110 OR #111 OR #112 OR #113 OR #114 OR #115 OR #115 OR #116 OR #117 OR #118 OR #119 OR #120 OR #121)

#123 (#32 OR #74 OR #90 OR #95 OR #107 OR #122)

#124 (#3 AND #123)

Appendix 2. MEDLINE search strategy

1. exp gout/

2. gout$.tw.

3. 1 or 2

4. exp life style/

5. (life adj2 (style$ or change$ or event$)).tw.

6. lifestyle$.tw.

7. social support/

8. social support.tw.

9. exp relaxation/ or relaxation therapy/

10. relax$.tw.

11. self efficacy/

12. (self adj (efficac$ or help or manag$ or care)).tw.

13. exp health promotion/

14. exp health education/

15. (health adj (promot$ or educat$)).tw.

16. (motivat$ adj (therap$ or interview$)).tw.

17. or/4-16

18. exp Weight Loss/

19. weight loss.tw.

20. (weight adj2 (lo$ or reduc$ or eliminat$)).tw.

21. ((body mass index or bmi) adj3 (los$ or reduc$ or decreas$ or low$)).tw.

22. (Waist circumference adj2 (reduc$ or low$ or small$)).tw.

23. (Waist size adj2 (reduc$ or low$ or small$)).tw.

24. energy restrict$.tw.

25. (calor$ adj2 (restrict$ or reduc$ or low$)).tw.

26. exp Anti-Obesity Agents/

27. (appetite adj2 suppress$).tw.

28. orlistat.tw.

29. xenical.tw.

30. alli.tw.

31. tetrahydrolipstatin.tw.

32. phentermine.tw.

33. phenyl-tertiary-butylamine.tw.

34. Ionamin.tw.

35. adipex-P.tw.

36. anoxine-AM.tw.

37. duromine.tw.

38. metermine.tw.

39. mirapront.tw.

40. obephen.tw.

41. obestin-30.tw.

42. phentremene.tw.

43. phentrol.tw.

44. phenterex.tw.

45. phentromin.tw.

46. pro-fast SA.tw.

47. redusa.tw.

48. panbesy.tw.

49. phentermine trenker.tw.

50. Obenix.tw.

51. Oby-trim.tw.

52. Teramine.tw.

53. Zantryl.tw.

54. Sinpet.tw.

55. Supremin.tw.

56. Umine.tw.

57. Weltmine.tw.

58. Aplenzin.tw.

59. or/18-58

60. exp diet/

61. diet$.tw.

62. exp Nutrition Therapy/

63. (lacto-vegetarian$ or lacto vegetarian$ or vegetarian$ or non-vegetarian$).tw.

64. (non adj2 vegetarian$).tw.

65. vegan$.tw.

66. (Cretan or Mediterranean).tw.

67. Fasting/

68. fast$.tw.

69. (protein adj2 (restrict$ or reduc$ or low$ or elim$)).tw.

70. (purine adj2 (restrict$ or reduc$ or low$ or elim$)).tw.

71. (fat adj2 (restrict$ or reduc$ or low$ or elim$)).tw.

72. (triglyceride adj2 (restrict$ or reduc$ or low$ or elim$)).tw.

73. (cholesterol adj2 (restrict$ or reduc$ or low$ or elim$)).tw.

74. (diet adj3 (reduc$ or low$ or restrict$ or elim$)).tw.

75. or/60-74

76. exp Dairy Products/

77. (milk or cheese$ or yog?urt or dairy).tw.

78. milk/ or cultured milk products/

79. or/76-78

80. exp Sucrose/

81. Fructose/

82. (sucrose$ or lactose$ or glucose$ or fructose$ or glycerine$ or lycerine$ or dextrose$ or aspartame$ or polycose$ or sacchar$ or sugar$).tw.

83. (sweet$ adj6 (solution$ or tast$)).tw.

84. (Diet$ adj3 (drink$ or beverage$)).tw.

85. (soft adj2 (drink$ or beverage$)).tw.

86. (sugar adj2 free adj2 (drink$ or beverage$)).tw.

87. (soda or sodas).tw.

88. or/80-87

89. Coffee/

90. Caffeine/

91. (coffee or caffiene or caffeinated or decaffeinated).tw.

92. or/89-91

93. exp Ethanol/

94. ethanol.tw.

95. exp Alcohol-Related Disorders/

96. Alcohol Drinking/

97. alcohol$.tw.

98. or/93-97

99. exp exercise/

100. exp Exercise Therapy/

101. exp Exercise Movement Techniques/

102. exp "Physical Education and Training"/

103. Physical Fitness/

104. Physical Exertion/

105. exp sports/

106. exercis$.tw.

107. sport$.tw.

108. (physical$ adj (fit$ or exert$ or activ$)).tw.

109. (run$ or jog$ or walk$).tw.

110. (swim$ or cycl$ or bicycl$).tw.

111. train$.tw.

112. kinesi?therap$.tw.

113. ((weight or muscle$) adj (strength$ or resistance)).tw.

114. endurance$.tw.

115. or/99-114

116. exp Tobacco/

117. "Tobacco Use Disorder"/

118. exp "Tobacco Use Cessation"/

119. Tobacco Smoke Pollution/

120. Nicotine/

121. smok$.tw.

122. (cigarette$ or cigar$ or pipe$).tw.

123. Nicotinic Agonists/

124. (nicotine adj (replacement or patch$ or gum or nasal)).tw.

125. nrt.tw.

126. nicorette.tw.

127. Nicotrol.tw.

128. Nicoderm$.tw.

129. Habitrol.tw.

130. Bupropion/

131. Bupropion.tw.

132. Amfebutamone.tw.

133. Aplenzin.tw.

134. Budeprion.tw.

135. Buproban.tw.

136. Butrew.tw.

137. Buxon.tw.

138. champix.tw.

139. Clorprax.tw.

140. Dosier.tw.

141. Elontril.tw.

142. Mondrian.tw.

143. Nicotex.tw.

144. Prexaton.tw.

145. Quomem.tw.

146. Voxra.tw.

147. Wellbutrin.tw.

148. Zetron.tw.

149. Zyban.tw.

150. Zyntabac.tw.

151. varenicline.tw.

152. exp hypnosis/

153. hypno$.tw.

154. exp counseling/

155. counsel$.tw.

156. or/116-155

157. or/17,59,75,79,88,92,98,115,156

158. 3 and 157

159. randomized controlled trial.pt.

160. controlled clinical trial.pt.

161. randomized.ab.

162. placebo.ab.

163. drug therapy.fs.

164. randomly.ab.

165. trial.ab.

166. groups.ab.

167. or/159-166

168. (animals not (humans and animals)).sh.

169. 167 not 168

170. 158 and 169

Appendix 3. EMBASE search strategy

1. exp gout/

2. gout$.tw.

3. 1 or 2

4. exp life style/

5. Lifestyle modification/

6. (life adj2 (style$ or change$ or event$)).tw.

7. lifestyle$.tw.

8. Social support/

9. social support.tw.

10. Relaxation training/

11. relax$.tw.

12. Self concept/ or exp self care/

13. (self adj (efficac$ or help or manag$ or care)).tw.

14. Health promotion/

15. exp health education/

16. (health adj (promot$ or educat$)).tw.

17. (motivat$ adj (therap$ or interview$)).tw.

18. 4 or 17

19. weight reduction/

20. (weight adj2 (lo$ or reduc$ or eliminat$)).tw.

21. ((body mass index or bmi) adj3 (los$ or reduc$ or decreas$ or low$)).tw.

22. (Waist circumference adj2 (reduc$ or low$ or small$)).tw.

23. (Waist size adj2 (reduc$ or low$ or small$)).tw.

24. energy restrict$.tw.

25. (calor$ adj2 (restrict$ or reduc$ or low$)).tw.

26. antiobesity agent/

27. (appetite adj2 suppress$).tw.

28. orlistat.tw.

29. xenical.tw.

30. alli.tw.

31. tetrahydrolipstatin.tw.

32. phentermine.tw.

33. phenyl-tertiary-butylamine.tw.

34. Ionamin.tw.

35. adipex-P.tw.

36. anoxine-AM.tw.

37. duromine.tw.

38. metermine.tw.

39. mirapront.tw.

40. obephen.tw.

41. obestin-30.tw.

42. phentremene.tw.

43. phentrol.tw.

44. phenterex.tw.

45. phentromin.tw.

46. pro-fast SA.tw.

47. redusa.tw.

48. panbesy.tw.

49. phentermine trenker.tw.

50. Obenix.tw.

51. Oby-trim.tw.

52. Teramine.tw.

53. Zantryl.tw.

54. Sinpet.tw.

55. Supremin.tw.

56. Umine.tw.

57. Weltmine.tw.

58. amfebutamone/

59. Aplenzin.tw.

60. Zyban.tw.

61. or/19-60

62. exp diet/

63. diet$.tw.

64. exp diet therapy/

65. (lacto-vegetarian$ or lacto vegetarian$ or vegetarian$ or non-vegetarian$).tw.

66. (non adj2 vegetarian$).tw.

67. vegan$.tw.

68. (Cretan or Mediterranean).tw.

69. fast$.tw.

70. (protein adj2 (restrict$ or reduc$ or low$ or elim$)).tw.

71. (purine adj2 (restrict$ or reduc$ or low$ or elim$)).tw.

72. (fat adj2 (restrict$ or reduc$ or low$ or elim$)).tw.

73. (triglyceride adj2 (restrict$ or reduc$ or low$ or elim$)).tw.

74. (cholesterol adj2 (restrict$ or reduc$ or low$ or elim$)).tw.

75. or/62-73

76. exp dairy product/

77. (milk or cheese$ or yog?urt or dairy).tw.

78. milk/

79. or/76-78

80. sucrose/

81. fructose/

82. (sucrose$ or lactose$ or glucose$ or fructose$ or glycerine$ or lycerine$ or dextrose$ or aspartame$ or polycose$ or sacchar$ or sugar$).tw.

83. (sweet$ adj6 (solution$ or tast$)).tw.

84. (Diet$ adj3 (drink$ or beverage$)).tw.

85. (soft adj2 (drink or beverage)).tw.

86. (sugar adj2 free adj2 (drink$ or beverage$)).tw.

87. (soda or sodas).tw.

88. or/80-87

89. coffee/

90. caffeine/

91. (coffee or caffiene or caffeinated or decaffeinated).tw.

92. or/89-91

93. alcohol/

94. ethanol.tw.

95. alcoholism/

96. drinking behavior/

97. alcohol$.tw.

98. or/93-97

99. exp exercise/

100. exp kinesiotherapy/

101. physical education/

102. fitness/

103. exp sports/

104. exercis$.tw.

105. sport$.tw.

106. (physical$ adj (fit$ or exert$ or activ$)).tw.

107. (run$ or jog$ or walk$).tw.

108. (swim$ or cycl$ or bicycl$).tw.

109. train$.tw.

110. kinesi?therap$.tw.

111. ((weight or muscle$) adj (strength$ or resistance)).tw.

112. endurance.tw.

113. or/99-112

114. tobacco/

115. tobacco dependence/

116. smoking cessation/

117. exp "smoking and smoking related phenomena"/

118. nicotine/

119. smok$.tw.

120. (cigarette$ or cigar$ or pipe$).tw.

121. nicotine replacement therapy/

122. (nicotine adj (replacement or patch$ or gum or nasal)).tw.

123. nrt.tw.

124. nicorette.tw.

125. Nicotrol.tw.

126. Nicoderm$.tw.

127. Habitrol.tw.

128. amfebutamone/

129. Bupropion.tw.

130. Amfebutamone.tw.

131. Aplenzin.tw.

132. Budeprion.tw.

133. Buproban.tw.

134. Butrew.tw.

135. Buxon.tw.

136. champix.tw.

137. Clorprax.tw.

138. Dosier.tw.

139. Elontril.tw.

140. Mondrian.tw.

141. Nicotex.tw.

142. Prexaton.tw.

143. Quomem.tw.

144. Voxra.tw.

145. Wellbutrin.tw.

146. Zetron.tw.

147. Zyban.tw.

148. Zyntabac.tw.

149. varenicline.tw.

150. hypnosis/

151. hypno$.tw.

152. exp counseling/

153. counsel$.tw.

154. or/114-153

155. or/18,61,75,79,88,92,98,113,154

156. 3 and 155

157. (random$ or placebo$ or single blind$ or double blind$ or triple blind$).ti,ab.

158. RETRACTED ARTICLE/

159. 157 or 158

160. (animal$ not human$).sh,hw.

161. (book or conference paper or editorial or letter or review).pt. not exp randomized controlled trial/

162. (random sampl$ or random digit$ or random effect$ or random survey or random regression).ti,ab. not exp randomized controlled trial/

163. 159 not (160 or 161 or 162)

164. 156 and 163

Contributions of authors

JM wrote the current version of the protocol. RB, CE and MS provided comments and suggestions on draft versions of the protocol, and all authors approved the current version.

Declarations of interest

None known

Sources of support

Internal sources

  • The Royal Melbourne Hospital, Australia.

    In kind support

  • Monash University, Australia.

    In kind support

  • Cabrini Hospital, Australia.

    In kind support

  • Southampton General Hospital, UK.

    In kind support

External sources

  • No sources of support supplied, Not specified.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Schlesinger 2002

Methods

Randomised controlled trial

Duration: one week

Withdrawals: nil

Sample size calculation: not stated

Intention-to-treat analysis: not performed

Participants

19 participants

Inclusion criteria:

- not reported

Exclusion criteria:

- not reported

Interventions

Intervention 1: topical ice therapy + oral prednisone 30mg tapered over 6 days (30mg x 2 days, 20mg x 2 days, 10mg x 2days) + colchicine 0.6 mg/day (n=10)

Intervention 2:oral prednisone 30 mg tapered over 6 days (30mg x 2 days, 20mg x 2 days, 10mg x 2days) + colchicine 0.6 mg/day (n=9)

Outcomes

Assessed at baseline and one week later:

1. pain (VAS)

2. circumference of the affected joint (cm)

3. synovial fluid WBC count

4. synovial fluid volume

NotesWe attempted to contact the trial author for information not reported in the trial (e.g., patient demographics, blinding, adverse events)
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "Patients were randomly assigned to one of 2 groups (by blindly drawing a folded paper note)."
Allocation concealment (selection bias)High riskComment: method of folding of paper note used for allocation concealment could easily have been tampered with
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: not described. Clarification was sought from the trial author but a reply was not received. Due to the nature of the intervention (ice) it is unlikely that participants could have been blinded
Blinding of outcome assessment (detection bias)
All outcomes
High riskComment: not described. Clarification was sought from the trial author but a reply was not received. Due to the nature of the intervention (ice) it is unlikely that participants could have been blinded
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: no study withdrawals, or excluded data
Selective reporting (reporting bias)Unclear riskComment: all pre-specified efficacy outcome data were reported. No adverse events described
Other biasUnclear riskComment: sources of funding not described, and trial not registered with clinical trials registry

Characteristics of studies awaiting assessment [ordered by study ID]

Zeng 2012

Methods 
Participants 
Interventions 
Outcomes 
NotesAwaiting translation

Zhao 2009

Methods 
Participants 
Interventions 
Outcomes 
NotesAwaiting translation

Ancillary